© 2017 The Association for the Publication of the Journal of Internal Medicine Background: Obesity is highly prevalent in African American women, especially those in the rural southern USA, resulting in persistent health disparities. Objective: To test the effectiveness of an evidence-based behavioural weight loss intervention delivered by community health advisors to African American women in the rural south. Design and Methods: Overweight or obese African American women (30–70 years) from eight counties in Mississippi and Alabama participated in a 24-month randomized controlled trial of an evidence-based behavioural weight loss programme augmented with community strategies to support healthy lifestyles (Weight Loss Plus, N = 154) compared to the weight loss programme alone (Weight Loss Only, N = 255). This study reports on 6-month outcomes on primary (weight change) and secondary (waist circumference, blood pressure, lipids, fasting blood glucose) outcomes, coinciding with the completion of the intensive weight loss phase. Results: Weight Loss Only participants lost an average of 2.2 kg (P < 0.001). Weight Loss Plus participants lost an average of 3.2 kg (P < 0.001). The proportion of the total sample that lost at least 5% of their body weight was 27.1% with no difference between treatment groups. Similarly, we observed statistically significant reductions in blood pressure, waist circumference and triglycerides in each treatment group, with no statistical differences between groups. Conclusion: Trained lay health staff and volunteers from the rural southern USA were able to deliver a translation of a high-intensity behavioural intervention targeted to African American women, resulting in clinically meaningful weight loss and improvement in other metabolic outcomes in a significant proportion of participants.